Role of Uridine Phosphorylase 1 in Cancer: A Comprehensive Pan-Cancer Analysis Highlighting Its Prognostic and Therapeutic Potential

Role of Uridine Phosphorylase 1 in Cancer: A Comprehensive Pan-Cancer Analysis Highlighting Its Prognostic and Therapeutic Potential | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Role of Uridine Phosphorylase 1 in Cancer: A Comprehensive Pan-Cancer Analysis Highlighting Its Prognostic and Therapeutic Potential Shuihong Yu, Tao Jiang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4446012/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Uridine phosphorylase 1 (UPP1), implicated as an oncogene, plays a pivotal role in the metabolism of pyrimidine nucleosides, which are crucial for cellular replication and tumor progression. Despite its importance, a systematic pan-cancer analysis of UPP1 has not been previously conducted. This study addresses this gap by evaluating UPP1's gene expression, genetic alterations, DNA methylation, and prognostic significance across 33 different cancer types, utilizing extensive bioinformatics resources, including TIMER, GEPIA, UALCAN, cBioPortal, and Kaplan–Meier Plotter. Our findings indicate that UPP1 is highly expressed in 19 cancer types and significantly down-regulated in four. Importantly, high levels of UPP1 are associated with adverse survival outcomes in eight types of cancer, highlighting its potential as a negative prognostic marker. The study also reveals that gene amplification is the predominant alteration of UPP1 in these cancers. Furthermore, variations in promoter methylation across cancers suggest a regulatory mechanism potentially influencing UPP1 expression. Our analysis also establishes a significant association between UPP1 expression and both tumor mutational burden (TMB) and microsatellite instability (MSI) in several cancers, as well as a correlation with the level of immune cell infiltration. This comprehensive pan-cancer analysis underscores the importance of UPP1 as both a prognostic biomarker and a possible therapeutic target, providing a foundational basis for further investigation into its roles in cancer biology and therapy. UPP1 Pan-Cancer Prognostic Biomarker Genetic Alterations DNA Methylation Immune Infiltration Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4446012","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":308887384,"identity":"1ac6ab49-7198-402c-ac03-5764c2677c80","order_by":0,"name":"Shuihong Yu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyklEQVRIiWNgGAWjYBACPgYG9g+J/9h4+NkbGx9+IEYLGwh9YOOTkew53GwsQawWxhlscjYGM9LbBHiI0sLeY/aYh8eMx0DyYRuDBIOdnG4DIS08Z8yNeSTSeMylE9seFDAkG5sdIKRFIi1BmsfgGI/l7MR2AwmGA4nbiNOS8J/H4ObBNgke4rQkH5OccYCNx+AGI7FaeA4fNvjYwMYj2ZMIDGQDIvwCisEHiQ1s9vzsxx8+/FBhJ0dQCxowIE35KBgFo2AUjAIcAADexDsnIF2jMAAAAABJRU5ErkJggg==","orcid":"","institution":"Anqing Medical College","correspondingAuthor":true,"prefix":"","firstName":"Shuihong","middleName":"","lastName":"Yu","suffix":""},{"id":308887385,"identity":"07560dc9-5838-4b39-9fa7-87943a220e81","order_by":1,"name":"Tao Jiang","email":"","orcid":"","institution":"Navy Anqing Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tao","middleName":"","lastName":"Jiang","suffix":""}],"badges":[],"createdAt":"2024-05-20 01:38:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4446012/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4446012/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":57710013,"identity":"05a09527-6180-4eaf-be03-1612e3e7d455","added_by":"auto","created_at":"2024-06-04 15:44:33","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1030582,"visible":true,"origin":"","legend":"","description":"","filename":"UPP1inCancerPrognosticandTherapeuticInsights1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4446012/v1_covered_a42e99cc-0aa3-49ff-bcbb-66e4cd3b79a9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Role of Uridine Phosphorylase 1 in Cancer: A Comprehensive Pan-Cancer Analysis Highlighting Its Prognostic and Therapeutic Potential","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"UPP1, Pan-Cancer, Prognostic Biomarker, Genetic Alterations, DNA Methylation, Immune Infiltration","lastPublishedDoi":"10.21203/rs.3.rs-4446012/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4446012/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eUridine phosphorylase 1 (UPP1), implicated as an oncogene, plays a pivotal role in the metabolism of pyrimidine nucleosides, which are crucial for cellular replication and tumor progression. 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Our analysis also establishes a significant association between UPP1 expression and both tumor mutational burden (TMB) and microsatellite instability (MSI) in several cancers, as well as a correlation with the level of immune cell infiltration. 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